Autoimmunity to the nuclear autoantigen DFS70 (LEDGF): What exactly are the autoantibodies trying to tell us?

Tumor-associated Antigen Arrays for the Serological Diagnosis of Cancer

“…Third, certain autoantibodies also lack specificity because they may arise as a consequence of molecular events that are commonly associated with both cancer and other diseases. This is illustrated by our own studies on autoimmunity to the stress-regulated survival protein LEDGF/p75 in which the autoantibodies were detected not only in a subset of patients with prostate cancer but also in chronic inflammatory conditions associated with aberrant cell death and ASCOS and even in healthy individuals (27,84,97). This led to the hypothesis that accumulation of LEDGF/p75 and its truncated variants in these diseases, due perhaps to a combination of up-regulation by oxidative stress and cleavage during cell death under a proinflammatory environment, could trigger loss of immune tolerance against the protein with ensuing production of autoantibodies (27,84,97).…”

“…This is illustrated by our own studies on autoimmunity to the stress-regulated survival protein LEDGF/p75 in which the autoantibodies were detected not only in a subset of patients with prostate cancer but also in chronic inflammatory conditions associated with aberrant cell death and ASCOS and even in healthy individuals (27,84,97). This led to the hypothesis that accumulation of LEDGF/p75 and its truncated variants in these diseases, due perhaps to a combination of up-regulation by oxidative stress and cleavage during cell death under a proinflammatory environment, could trigger loss of immune tolerance against the protein with ensuing production of autoantibodies (27,84,97). We and others also reported that autoantibodies to the mitosis and cell proliferation autoantigen CENP-F are present not only in certain patients with cancer but also in patients with non-malignant disorders associated with increased cell proliferation (53,54).…”

“…This domain has been implicated in DNA binding and transcription function (93), survival function (93,94), binding to human immunodeficiency virus integrase (95), and autoantibody recognition (96). It should be emphasized that anti-LEDGF/p75 antibodies are not specific for prostate cancer because they have been also detected, albeit at relatively low frequencies and titers, in "healthy individuals" and patients with various human inflammatory conditions (97). We suggested that autoantibodies to LEDGF/p75 could be considered as reporters of the up-regulation of this protein by inflammation and ASCOS in cancer and other inflammatory conditions (27,97).…”

Clinical significance of anti-dense fine speckled 70 antibody in patients with fibromyalgia

“…Anti-DFS70 antibodies were initially identified in a patient with interstitial cystitis [14] but were later associated with various conditions, especially atopic dermatitis [15]. Since their first description, anti-DFS70 antibodies have been found in the sera of patients with a variety of conditions including cancer [16], and even more interestingly in HI [13,17].…”

“…Dellavance et al evaluated over 10,000 ANA positive samples by HEp-2 IIF followed by a confirmatory immunoblot and reported that anti-DFS70 antibodies were common among ANA-positive individuals with no evidence of SARD and that among autoimmune patients with this autoantibody over a half had evidence of autoimmune thyroiditis [18]. Although the spectrum of clinical associations and the mechanisms of anti-DFS70 induction are still unclear, different research teams have confirmed that anti-DFS70 antibodies are curiously more prevalent in apparently HI than in SARD patients [13,15]. In addressing the prognostic and long-term outcome of individuals that have anti-DFS70 antibodies, it was recently reported that none of the 40 anti-DFS70 positive HI developed SARD over an average of 4-years of clinical followup [12].…”